Extracellular Vesicles From Mesenchymal Cells in the Treatment of Acute Respiratory Failure

NCT06002841 | Unknown Phase 1 DMC

• 1 other identifier: EVs_2023
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase I/II, randomized, double-blind, placebo-controlled clinical trial that will evaluate the safety and potential efficacy of therapy with extracellular vesicles (EVs) obtained from mesenchymal stromal cells (MSCs), patients with moderate to severe acute respiratory distress syndrome due to COVID-19 or other etiology. Participants will be allocated to receive EVs obtained from MSCs or placebo (equal volume of Plasma-Lyte A). Blinding will cover the participants, the multidisciplinary intensive care team and the investigators.

Conditions

Severe Acute Respiratory Syndrome (SARS); Acute Respiratory Distress Syndrome (ARDS); Pneumonia

Keywords

SARS-CoV-2; intravenous therapy; extracellular vesicles; ARDS; mesenchymal cells

Outcome Measures

Primary Outcomes (1)

• Measure administration of extracellular vesicles (EVs) up to 28 days

  Measure as reported adverse events up to 28 days after treatment or placebo administration to evaluate safety of treatment

  28 days

Secondary Outcomes (6)

• All-cause mortality

  Day 14 and day 28

• Variation in the Ratio PaO2/FiO2

  Baseline, day 01, day 02 and day 07

• Variation in the SOFA index

  day 01, day 02, day 07, day 09, day 14 and day 29

• Exploratory laboratory analysis

  30 days

• Duration of the period of hospitalization

  30 days

Study Arms (2)

EV group

EXPERIMENTAL

will consist of 10 participants who will receive two infusions of 25 mL of the investigational product (Plasma-Lyte A solution containing EVs obtained from MSCs), intravenously, at intervals of 48 h.

Biological: intravenous treatment with EVs

Placebo group

PLACEBO COMPARATOR

will consist of 5 participants who will receive an equal volume of Plasma-Lyte A, intravenously, following the same schedule as the IV group: two infusions with an interval of 48 hours.

Biological: intravenous treatment with placebo solution

Interventions

intravenous treatment with EVs BIOLOGICAL

intravenous treatment with extracellular vesicles

EV group

intravenous treatment with placebo solution BIOLOGICAL

intravenous treatment with placebo solution (without extracellular vesicles)

Placebo group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>= 18 years old;
• Chest CT radiological image with ground-glass opacities or chest X-ray with - bilateral infiltrates characteristic of pulmonary edema;
• In invasive mechanical ventilation with PEEP 5 cm H2O and PaO2/FiO2\<250mmHg;
• Respiratory failure not explained by cardiac causes or fluid overload.

You may not qualify if:

• Unable to provide informed consent;
• Pregnancy or breastfeeding;
• Patients with active malignancy who have received chemotherapy in the last 2 years;
• Life expectancy of less than 6 months or in exclusive palliative care;
• Severe liver failure, with a Child-Pugh score \> 12;
• Previous renal failure: patients already undergoing dialysis or patients with GFR \< 30ml/min/1.73 m2
• Clinical or radiological suspicion of tuberculosis;
• Chronic respiratory failure;
• Use of ECMO;
• Moribund (high probability of death within the next 48 hours).

Sponsors & Collaborators

• D'Or Institute for Research and Education: lead
• Hospital Sao Rafael: collaborator
• Rio de Janeiro State Research Supporting Foundation (FAPERJ): collaborator
• Oswaldo Cruz Foundation: collaborator

Study Sites (1)

Hospital São Rafael

Salvador, Estado de Bahia, 41253-190, Brazil

Location

Related Publications (19)

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  PMID: 34136481 BACKGROUND

• de Castro LL, Xisto DG, Kitoko JZ, Cruz FF, Olsen PC, Redondo PAG, Ferreira TPT, Weiss DJ, Martins MA, Morales MM, Rocco PRM. Human adipose tissue mesenchymal stromal cells and their extracellular vesicles act differentially on lung mechanics and inflammation in experimental allergic asthma. Stem Cell Res Ther. 2017 Jun 24;8(1):151. doi: 10.1186/s13287-017-0600-8.

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• Cruz FF, Borg ZD, Goodwin M, Sokocevic D, Wagner DE, Coffey A, Antunes M, Robinson KL, Mitsialis SA, Kourembanas S, Thane K, Hoffman AM, McKenna DH, Rocco PR, Weiss DJ. Systemic Administration of Human Bone Marrow-Derived Mesenchymal Stromal Cell Extracellular Vesicles Ameliorates Aspergillus Hyphal Extract-Induced Allergic Airway Inflammation in Immunocompetent Mice. Stem Cells Transl Med. 2015 Nov;4(11):1302-16. doi: 10.5966/sctm.2014-0280. Epub 2015 Sep 16.

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• Silva JD, de Castro LL, Braga CL, Oliveira GP, Trivelin SA, Barbosa-Junior CM, Morales MM, Dos Santos CC, Weiss DJ, Lopes-Pacheco M, Cruz FF, Rocco PRM. Mesenchymal Stromal Cells Are More Effective Than Their Extracellular Vesicles at Reducing Lung Injury Regardless of Acute Respiratory Distress Syndrome Etiology. Stem Cells Int. 2019 Aug 21;2019:8262849. doi: 10.1155/2019/8262849. eCollection 2019.

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MeSH Terms

Conditions

Severe Acute Respiratory Syndrome; Respiratory Distress Syndrome; Pneumonia

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Respiration Disorders

Study Officials

• Bruno Souza, M.D

  Instituto D'Or de Pesquisa e Ensino (IDOR), Salvador, Brazil

  PRINCIPAL INVESTIGATOR

• Patrícia Rocco, M.D

  Universidade Federal do Rio de Janeiro (UFRJ)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Carolina Nonaka, phD

CONTACT

+55 (71) 3281-6970; carolina.nonaka@hsr.com.br

Ingrid Barbosa, B.Sc

CONTACT

+551121098855; nape@idor.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The treatment and placebo solutions will be indistinguishable in terms of their appearance. Stringent protocols will be established to guarantee that the physicians responsible for assessing patient safety, evaluating efficacy outcomes, and conducting laboratory analyses will be blinded to the randomization codes.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Parallel Assignment

Study Record Dates

• First Submitted: July 27, 2023
• First Posted: August 21, 2023
• Study Start: February 1, 2024
• Primary Completion: June 1, 2025
• Study Completion: June 1, 2025
• Last Updated: August 21, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)